ESC®️ 2025 – Beyond Traditional Risk Factors: The Weight of Inflammation

At ESC®️ 2025, Paul Ridker emphasized that the traditional assessment of cardiovascular risk factors — hypertension, dyslipidemia, diabetes, and smoking — does not adequately account for a relevant portion of the population, particularly women, who experience cardiovascular events despite lacking these elements. These individuals are classified as SMuRF-less.

The study presented, based on the Women’s Health Study cohort of 12,530 initially healthy women followed for 30 years, demonstrated that inflammation, measured by high-sensitivity C-reactive protein (hsCRP), is an independent determinant of cardiovascular risk in this group.

Results showed that SMuRF-less women with hsCRP above 3 mg/L had a 77% higher risk of coronary heart disease, 39% higher risk of ischemic stroke, and 52% higher risk of total cardiovascular events, compared with those whose hsCRP was below 1 mg/L. Notably, these risks persisted even after adjustment for body mass index and glomerular filtration rate.

During the interview, Ridker highlighted that these patients would not be identified by traditional risk stratification algorithms, underscoring the limitations of current primary prevention guidelines. He further emphasized that analysis from the JUPITER trial, which evaluated rosuvastatin use in individuals with elevated hsCRP, demonstrated a 38% reduction in major cardiovascular events within this patient profile.

Ridker stressed the need to incorporate inflammation as a universal therapeutic target, similar to the current approach for LDL cholesterol and blood pressure. He also underlined the importance of considering early preventive strategies in women, who are traditionally underdiagnosed and undertreated, proposing broader discussions on the initiation of therapies such as statins in this subgroup.

In conclusion, the “SMuRF-less but inflamed” category represents an emerging concept in preventive cardiology, with direct implications for risk reclassification and the implementation of therapies targeting inflammatory biology, thereby expanding the scope of cardiovascular prevention.

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